A drug repurposing study based on clinical big data for the protective role of vitamin D in olanzapine-induced dyslipidemia

概要

Schizophrenia includes a series of mental disorders like hallucinations, reduced
motivation, delusions, and either negative or positive symptoms [1]. Currently, the most
effective intervention is the treatment by atypical antipsychotics, also known as secondgeneration antipsychotics, which act by inhibiting the actions of dopamine D2 receptors
and serotonin 5-HT2A receptors [2]. Among them, olanzapine is one of the most widely
applied agents [3]. However, dyslipidemia has been clinically reported to be a typical
adverse effect of olanzapine treatment, characterized by symptoms such as increased
body mass and increased serum levels of total cholesterol and triglycerides [4]. A recently
published study on the adverse effects of olanzapine further confirmed that olanzapine
could induce LDL cholesterol level increase in the blood [5]. Although olanzapine is
pharmacologically considered cardiac-safe, its indirect promotion of atherosclerosis by
raising blood lipid content makes it a cardiovascular risk factor [6-8]. These defects even
make olanzapine a contributor to excessive premature mortality [9]. Up to now, the
preliminary clarification on the mechanism behind olanzapine-induced dyslipidemia
makes it impossible to develop treatment or prevention methods with clinical significance
[10]. Thus, there is an emerging demand for exploring novel drug target screening
approaches.
In consideration of saving time and cost, drug-repurposing is recognized as an
economical approach to refine new potential therapeutic applications from marketaccessible drugs [11]. Besides, without the development of new agents from
unprecedented compounds, clinical safety has already been validated by historical earlystage trials in the drug-repurposing practice [12, 13]. ...

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